The general objective of this project is to carry out a complete morphological description of the nervous system of a simple organism during its embryological development and to study the way in which this development can be altered by genetic and environmental factors. We have developed optical and computer methods which allow thousands of electron or light micrographs of serial brain sections to be combined and analyzed in a way which permits the computer to be used as a very large three-dimensional notebook. A three-dimensional map of the brain can be constructed in the computer, and this mapping repeated a sequence of times during the development of the embryo. These three-dimensional reconstructions have allowed us to detect several new phenomena associated with growing nerve fibers and the cells they contact. We propose to examine these phenomena and their significance in greater detail both morphologically and by experimental modification of growing embryos. Our ability to detect small changes in the nervous system, as well as our ability to select variant organisms by means of their altered behavior, should make it possible to study the chemical and physical induction of birth defects (teratogenesis) even when the agents are present at a very low dose. These studies would be of theoretical importance in understanding the mechanism of action of teratogens, as well as of practical importance for the question of evaluating the public health impact of low level environmental contamination. Finally, we plan to isolate genetic variants which will be selected as temperature-sensitive developmental mutants. In this way, we hope to study the mechanism by which genes control the developmental pattern of a nervous system.